The long term objectives and specific aims of this project are twofold; a) to further our ongoing research project in the synthesis and detailed studies of mono-and multi-nuclear transition metal complexes in an attempt to mimic aspects of the active sites of the hydrolytic enzymes and contribute toward the effort to understand the mechanisms of enzymatic catalysis, and; b) equally importantly, to recruit, involve, and train minority graduate and undergraduate students in the medical/biologically related chemical research as part of their training as prospective professionals in the biomedical field of research. The hydrolytic metallo-enzymes play crucial roles in the metabolism of all living organisms and hence there is a need to understand their mechanism of general and specific but always highly efficient, catalysis of vital reactions such as the hydrolysis of biomolecules such as DNA, RNA, carbohydrates, fats, and proteins. It is proposed to synthesize a range of rationally designed and progressively modified ligands and their Zn(II), Ni(II), and Cu(II) complexes, purify and study in detail their X-ray crystallographic structure, spectroscopic properties, and their acid-based and metal complex stability equilibria in Aqueous solutions under various conditions of solvents and pH. Detailed studies will be carried out of the catalytic properties these complexes initially for the hydrolysis of small molecules with biologically relevant functional groups such as phosphate and carboxylic acid esters and peptide (amide) bonds and at later stages actual biological molecules. Catalytic reaction products will be identified, the kinetics of the reactions studied, and investigations made into the relationship of the ligand and metal complex characteristics to the catalytic properties and how these findings help in understanding the enzymes. Student Participation and training in scientific research: Our equally emphasized focus and aim for this project is the training of minority undergraduate and graduate students in the techniques and methodology in the chemical research field related to chemical/biological and medical fields. We aim to recruit promising graduate and undergraduate minority students within howard university and from other schools and colleges at the early stages of their studies to involve students in our ongoing research work with active guided participation of students at every stage of the work from literature studies, design of experiments, executing experiments, interpreting data and communicating research finding in seminars and in publications. That has been the track record of the research group and it will be continued with the financial support obtained.